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Q92574 (TSC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hamartin
Alternative name(s):
Tuberous sclerosis 1 protein
Gene names
Name:TSC1
Synonyms:KIAA0243, TSC
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1164 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

In complex with TSC2, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Seems not to be required for TSC2 GAP activity towards RHEB. Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling. Ref.10 Ref.11

Subunit structure

Interacts with TSC2, leading to stabilize TSC2. In the absence of TSC2, TSC1 self-aggregates. Interacts with DOCK7. Interacts with FBXW5 and TBC1D7. Ref.7 Ref.8 Ref.9 Ref.12 Ref.13 Ref.14 Ref.16

Subcellular location

Cytoplasm. Membrane; Peripheral membrane protein. Note: At steady state found in association with membranes. Ref.7

Tissue specificity

Highly expressed in skeletal muscle, followed by heart, brain, placenta, pancreas, lung, liver and kidney. Also expressed in embryonic kidney cells.

Domain

The C-terminal putative coiled-coil domain is necessary for interaction with TSC2.

Post-translational modification

Phosphorylation at Ser-505 does not affect interaction with TSC2.

Involvement in disease

Tuberous sclerosis 1 (TSC1) [MIM:191100]: An autosomal dominant multi-system disorder that affects especially the brain, kidneys, heart, and skin. It is characterized by hamartomas (benign overgrowths predominantly of a cell or tissue type that occurs normally in the organ) and hamartias (developmental abnormalities of tissue combination). Clinical manifestations include epilepsy, learning difficulties, behavioral problems, and skin lesions. Seizures can be intractable and premature death can occur from a variety of disease-associated causes.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.22 Ref.24 Ref.26 Ref.27 Ref.29 Ref.32 Ref.33

Focal cortical dysplasia of Taylor balloon cell type (FCDBC) [MIM:607341]: Subtype of cortical dysplasias linked to chronic intractable epilepsy. Cortical dysplasias display a broad spectrum of structural changes, which appear to result from changes in proliferation, migration, differentiation, and apoptosis of neuronal precursors and neurons during cortical development.
Note: The disease may be caused by mutations affecting the gene represented in this entry. Ref.30

Ontologies

Keywords
   Cellular componentCytoplasm
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Epilepsy
Tumor suppressor
   DomainCoiled coil
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of Rho GTPase activity

Inferred from direct assay PubMed 10806479. Source: UniProtKB

cardiac muscle cell differentiation

Inferred from electronic annotation. Source: Ensembl

cell cycle arrest

Traceable author statement. Source: Reactome

cell projection organization

Inferred from electronic annotation. Source: Ensembl

cell-matrix adhesion

Inferred from mutant phenotype PubMed 10806479. Source: UniProtKB

cerebral cortex development

Inferred from electronic annotation. Source: Ensembl

hippocampus development

Inferred from electronic annotation. Source: Ensembl

insulin receptor signaling pathway

Traceable author statement. Source: Reactome

kidney development

Inferred from electronic annotation. Source: Ensembl

myelination

Inferred from electronic annotation. Source: Ensembl

negative regulation of TOR signaling

Inferred from mutant phenotype PubMed 17308101. Source: UniProtKB

negative regulation of cell proliferation

Inferred from mutant phenotype PubMed 10915759. Source: UniProtKB

negative regulation of cell size

Inferred from electronic annotation. Source: Ensembl

negative regulation of insulin receptor signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of translation

Inferred from mutant phenotype PubMed 17308101. Source: UniProtKB

neural tube closure

Inferred from electronic annotation. Source: Ensembl

positive regulation of focal adhesion assembly

Inferred from direct assay PubMed 10806479. Source: UniProtKB

potassium ion transport

Inferred from electronic annotation. Source: Ensembl

protein heterooligomerization

Inferred from electronic annotation. Source: Ensembl

protein stabilization

Inferred from direct assay PubMed 11175345. Source: UniProtKB

rRNA export from nucleus

Inferred from mutant phenotype PubMed 17308101. Source: UniProtKB

regulation of cell cycle

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of cell-matrix adhesion

Inferred from mutant phenotype PubMed 10806479. Source: UniProtKB

regulation of phosphoprotein phosphatase activity

Inferred from mutant phenotype PubMed 17308101. Source: UniProtKB

regulation of protein kinase activity

Inferred from electronic annotation. Source: Ensembl

regulation of stress fiber assembly

Inferred from direct assay PubMed 10806479. Source: UniProtKB

regulation of translation

Inferred from direct assay PubMed 17308101. Source: UniProtKB

response to insulin

Inferred from direct assay PubMed 16996505. Source: UniProtKB

synapse organization

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentTSC1-TSC2 complex

Inferred from direct assay Ref.8. Source: UniProtKB

cell cortex

Inferred from direct assay PubMed 10806479. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.8. Source: UniProtKB

cytosol

Inferred from direct assay Ref.9. Source: UniProtKB

growth cone

Inferred from electronic annotation. Source: Ensembl

intracellular membrane-bounded organelle

Inferred from electronic annotation. Source: Ensembl

lamellipodium

Inferred from direct assay PubMed 10806479. Source: UniProtKB

membrane

Inferred from direct assay PubMed 16636147. Source: UniProtKB

protein complex

Inferred from direct assay Ref.9. Source: UniProtKB

   Molecular_functionGTPase regulator activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

chaperone binding

Inferred from physical interaction Ref.9. Source: UniProtKB

protein N-terminus binding

Inferred from physical interaction PubMed 10806479PubMed 12226091. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.9Ref.14Ref.16Ref.8. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q92574-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q92574-2)

The sequence of this isoform differs from the canonical sequence as follows:
     70-120: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11641164Hamartin
PRO_0000065651

Regions

Coiled coil721 – 997277 Potential
Compositional bias1034 – 10374Poly-Gly
Compositional bias1038 – 10436Poly-Ser

Amino acid modifications

Modified residue5051Phosphoserine Ref.12 Ref.18 Ref.20
Modified residue5111Phosphoserine Ref.18
Modified residue5981Phosphoserine Ref.18

Natural variations

Alternative sequence70 – 12051Missing in isoform 2.
VSP_042890
Natural variant511E → D in TSC1; unknown pathological significance.
VAR_009397
Natural variant611L → R in TSC1; unknown pathological significance; reduced expression; altered subcellular localization; reduced inhibition of TORC1 signaling. Ref.33
VAR_070636
Natural variant681H → R in a bladder tumor; somatic mutation; reduced stability; does not affect interaction with TSC2. Ref.31
VAR_054386
Natural variant721L → P in TSC1. Ref.24
VAR_054387
Natural variant1171L → P in TSC1; reduced expression; altered subcellular localization; reduced interaction with TSC2; reduced inhibition of TORC1 signaling. Ref.32 Ref.33
VAR_070637
Natural variant1261V → I in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. Ref.33
VAR_070638
Natural variant1281Missing in TSC1; reduced expression; reduced inhibition of TORC1 signaling. Ref.32
VAR_070639
Natural variant1321G → D in TSC1; unknown pathological significance; reduced expression; altered subcellular localization; reduced inhibition of TORC1 signaling. Ref.33
VAR_070640
Natural variant1331V → I in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. Ref.33
VAR_070641
Natural variant1581F → C in a bladder tumor; somatic mutation; reduced stability; does not affect interaction with TSC2. Ref.31
VAR_054388
Natural variant1581F → S in a patient suspected of having tuberous sclerosis; unknown pathological significance; reduced expression; altered subcellular localization; reduced inhibition of TORC1 signaling. Ref.33
VAR_070642
Natural variant1801L → P in TSC1; reduced expression; reduced inhibition of TORC1 signaling. Ref.32
VAR_070643
Natural variant1901R → S.
VAR_009398
Natural variant1911L → H in TSC1; reduced expression; reduced inhibition of TORC1 signaling. Ref.32
VAR_009399
Natural variant198 – 1992NF → I in TSC1; reduced expression; altered subcellular localization; reduced interaction with TSC2; reduced inhibition of TORC1 signaling.
VAR_009400
Natural variant2041R → P in a patient suspected of having tuberous sclerosis; reduced expression; altered subcellular localization; reduced inhibition of TORC1 signaling. Ref.33
VAR_070644
Natural variant2061H → D in a bladder tumor; somatic mutation; reduced stability; does not affect interaction with TSC2. Ref.31
VAR_054389
Natural variant2161F → L in a bladder tumor; diffuse punctate cytoplasmic distribution in aminoacid-starved conditions; does not affect interaction with TSC2. Ref.31
VAR_054390
Natural variant2241M → R in TSC1; reduced expression; reduced inhibition of TORC1 signaling. Ref.32
VAR_009401
Natural variant2461R → K in TSC1; unknown pathological significance; no effect on expression; no effect on inhibition of TORC1 signaling. Ref.32
VAR_070645
Natural variant3051G → R in TSC1; unknown pathological significance; no effect on expression; no effect on inhibition of TORC1 signaling. Ref.32
VAR_070646
Natural variant3051G → W in TSC1; unknown pathological significance; no effect on expression; no effect on inhibition of TORC1 signaling. Ref.32
VAR_070647
Natural variant3221M → T. Ref.22 Ref.23 Ref.25 Ref.26 Ref.28
Corresponds to variant rs1073123 [ dbSNP | Ensembl ].
VAR_009402
Natural variant3361R → Q in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. Ref.33
VAR_070648
Natural variant3621P → S in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. Ref.33
VAR_070649
Natural variant4111L → I in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. Ref.33
VAR_070650
Natural variant4171T → I in TSC1; unknown pathological significance; does not affect interaction with TSC2. Ref.26 Ref.28 Ref.31
Corresponds to variant rs77464996 [ dbSNP | Ensembl ].
VAR_009403
Natural variant4481P → S in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. Ref.33
VAR_070651
Natural variant5001R → Q in TSC1. Ref.29
VAR_054391
Natural variant5091R → Q Rare polymorphism; no effect on expression; no effect on inhibition of TORC1 signaling. Ref.32
VAR_070652
Natural variant5231A → P in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. Ref.33
VAR_070653
Natural variant5671A → V in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. Ref.33
VAR_070654
Natural variant5771E → D. Ref.28
VAR_009404
Natural variant586 – 5894CKIP → S in TSC1.
VAR_009405
Natural variant5871K → R. Ref.1 Ref.23
Corresponds to variant rs118203576 [ dbSNP | Ensembl ].
VAR_009406
Natural variant6541Q → E in TSC1. Ref.26
Corresponds to variant rs75820036 [ dbSNP | Ensembl ].
VAR_009407
Natural variant6931D → H in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. Ref.33
VAR_070655
Natural variant6981L → R in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. Ref.33
VAR_070656
Natural variant7011Q → H in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. Ref.33
VAR_070657
Natural variant7261A → E in TSC1. Ref.22
VAR_009408
Natural variant7321H → Y in FCDBC; unknown pathological significance. Ref.22 Ref.23 Ref.25 Ref.30
Corresponds to variant rs118203657 [ dbSNP | Ensembl ].
VAR_009409
Natural variant7621N → S in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. Ref.33
VAR_070658
Natural variant8091E → Q. Ref.25
VAR_009410
Natural variant8111R → G in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. Ref.33
VAR_070659
Natural variant8291S → R. Ref.28
VAR_009411
Natural variant8831A → T in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. Ref.33
VAR_070660
Natural variant8991T → S in TSC1. Ref.26
VAR_009412
Natural variant9781L → V in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. Ref.33
VAR_070661
Natural variant10351G → S Rare polymorphism; no effect on expression; no effect on inhibition of TORC1 signaling. Ref.22 Ref.23 Ref.32
Corresponds to variant rs118203742 [ dbSNP | Ensembl ].
VAR_009413
Natural variant10431Missing in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. Ref.33
VAR_070662
Natural variant10971R → H Rare polymorphism; no effect on expression; no effect on inhibition of TORC1 signaling. Ref.32
VAR_070663
Natural variant11081G → S. Ref.23
VAR_009414
Natural variant11461D → Y in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. Ref.33
VAR_070664

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1998. Version 2.
Checksum: EF15509385C7AACC

FASTA1,164129,767
        10         20         30         40         50         60 
MAQQANVGEL LAMLDSPMLG VRDDVTAVFK ENLNSDRGPM LVNTLVDYYL ETSSQPALHI 

        70         80         90        100        110        120 
LTTLQEPHDK HLLDRINEYV GKAATRLSIL SLLGHVIRLQ PSWKHKLSQA PLLPSLLKCL 

       130        140        150        160        170        180 
KMDTDVVVLT TGVLVLITML PMIPQSGKQH LLDFFDIFGR LSSWCLKKPG HVAEVYLVHL 

       190        200        210        220        230        240 
HASVYALFHR LYGMYPCNFV SFLRSHYSMK ENLETFEEVV KPMMEHVRIH PELVTGSKDH 

       250        260        270        280        290        300 
ELDPRRWKRL ETHDVVIECA KISLDPTEAS YEDGYSVSHQ ISARFPHRSA DVTTSPYADT 

       310        320        330        340        350        360 
QNSYGCATST PYSTSRLMLL NMPGQLPQTL SSPSTRLITE PPQATLWSPS MVCGMTTPPT 

       370        380        390        400        410        420 
SPGNVPPDLS HPYSKVFGTT AGGKGTPLGT PATSPPPAPL CHSDDYVHIS LPQATVTPPR 

       430        440        450        460        470        480 
KEERMDSARP CLHRQHHLLN DRGSEEPPGS KGSVTLSDLP GFLGDLASEE DSIEKDKEEA 

       490        500        510        520        530        540 
AISRELSEIT TAEAEPVVPR GGFDSPFYRD SLPGSQRKTH SAASSSQGAS VNPEPLHSSL 

       550        560        570        580        590        600 
DKLGPDTPKQ AFTPIDLPCG SADESPAGDR ECQTSLETSI FTPSPCKIPP PTRVGFGSGQ 

       610        620        630        640        650        660 
PPPYDHLFEV ALPKTAHHFV IRKTEELLKK AKGNTEEDGV PSTSPMEVLD RLIQQGADAH 

       670        680        690        700        710        720 
SKELNKLPLP SKSVDWTHFG GSPPSDEIRT LRDQLLLLHN QLLYERFKRQ QHALRNRRLL 

       730        740        750        760        770        780 
RKVIKAAALE EHNAAMKDQL KLQEKDIQMW KVSLQKEQAR YNQLQEQRDT MVTKLHSQIR 

       790        800        810        820        830        840 
QLQHDREEFY NQSQELQTKL EDCRNMIAEL RIELKKANNK VCHTELLLSQ VSQKLSNSES 

       850        860        870        880        890        900 
VQQQMEFLNR QLLVLGEVNE LYLEQLQNKH SDTTKEVEMM KAAYRKELEK NRSHVLQQTQ 

       910        920        930        940        950        960 
RLDTSQKRIL ELESHLAKKD HLLLEQKKYL EDVKLQARGQ LQAAESRYEA QKRITQVFEL 

       970        980        990       1000       1010       1020 
EILDLYGRLE KDGLLKKLEE EKAEAAEAAE ERLDCCNDGC SDSMVGHNEE ASGHNGETKT 

      1030       1040       1050       1060       1070       1080 
PRPSSARGSS GSRGGGGSSS SSSELSTPEK PPHQRAGPFS SRWETTMGEA SASIPTTVGS 

      1090       1100       1110       1120       1130       1140 
LPSSKSFLGM KARELFRNKS ESQCDEDGMT SSLSESLKTE LGKDLGVEAK IPLNLDGPHP 

      1150       1160 
SPPTPDSVGQ LHIMDYNETH HEHS 

« Hide

Isoform 2 [UniParc].

Checksum: 6EA012443870A73C
Show »

FASTA1,113124,015

References

« Hide 'large scale' references
[1]"Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34."
van Slegtenhorst M.A., de Hoogt R., Hermans C., Nellist M., Janssen B., Verhoef S., Lindhout D., van den Ouweland A.M.W., Halley D.J.J., Young J., Burley M., Jeremiah S., Woodward K., Nahmias J., Fox M., Ekong R., Osborne J., Wolfe J. expand/collapse author list , Povey S., Snell R.G., Cheadle J.P., Jones A.C., Tachataki M., Ravine D., Sampson J.R., Reeve M.P., Richardson P., Wilmer F., Munro C., Hawkins T.L., Sepp T., Ali J.B.M., Ward S., Green A.J., Yates J.R.W., Kwiatkowska J., Henske E.P., Short M.P., Haines J.H., Jozwiak S., Kwiatkowski D.J.
Science 277:805-808(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-587.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Testis.
[3]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain."
Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N.
DNA Res. 3:321-329(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 466-1164 (ISOFORM 1/2).
Tissue: Bone marrow.
[6]"A silent mutation 1947 T-->C in exon 15 of TSC1 in Chinese."
Fang L., Wang N., Murong S.X., Wu Z.Y., Lin M.T.
Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 568-586.
[7]"Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles."
Plank T.L., Yeung R.S., Henske E.P.
Cancer Res. 58:4766-4770(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH TSC2.
[8]"Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products."
van Slegtenhorst M.A., Nellist M., Nagelkerken B., Cheadle J.P., Snell R.G., van den Ouweland A.M.W., Reuser A., Sampson J.R., Halley D.J.J., van der Sluijs P.
Hum. Mol. Genet. 7:1053-1057(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TSC2.
[9]"Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin."
Nellist M., van Slegtenhorst M.A., Goedbloed M., van den Ouweland A.M.W., Halley D.J.J., van der Sluijs P.
J. Biol. Chem. 274:35647-35652(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TSC2.
[10]"Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling."
Tee A.R., Fingar D.C., Manning B.D., Kwiatkowski D.J., Cantley L.C., Blenis J.
Proc. Natl. Acad. Sci. U.S.A. 99:13571-13576(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity."
Li Y., Inoki K., Guan K.-L.
Mol. Cell. Biol. 24:7965-7975(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Phosphorylation and binding partner analysis of the TSC1-TSC2 complex."
Nellist M., Burgers P.C., van den Ouweland A.M.W., Halley D.J.J., Luider T.M.
Biochem. Biophys. Res. Commun. 333:818-826(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-505, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH DOCK7 AND TSC2.
[13]"TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the HERC1 ubiquitin ligase."
Chong-Kopera H., Inoki K., Li Y., Zhu T., Garcia-Gonzalo F.R., Rosa J.L., Guan K.-L.
J. Biol. Chem. 281:8313-8316(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TSC2.
[14]"Identification of TBC7 having TBC domain as a novel binding protein to TSC1-TSC2 complex."
Nakashima A., Yoshino K., Miyamoto T., Eguchi S., Oshiro N., Kikkawa U., Yonezawa K.
Biochem. Biophys. Res. Commun. 361:218-223(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TBC1D7.
[15]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[16]"WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase."
Hu J., Zacharek S., He Y.J., Lee H., Shumway S., Duronio R.J., Xiong Y.
Genes Dev. 22:866-871(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FBXW5.
[17]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[18]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-505; SER-511 AND SER-598, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[19]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-505, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[21]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]"Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis."
Jones A.C., Daniells C.E., Snell R.G., Tachataki M., Idziaszczyk S.A., Krawczak M., Sampson J.R., Cheadle J.P.
Hum. Mol. Genet. 6:2155-2161(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TSC1 GLU-726, VARIANTS THR-322; TYR-732 AND SER-1035.
Tissue: Peripheral blood.
[23]"Comprehensive mutational analysis of the TSC1 gene: observations on frequency of mutation, associated features, and nonpenetrance."
Kwiatkowska J., Jozwiak S., Hall F., Henske E.P., Haines J.L., McNamara P., Braiser J., Wigowska-Sowinska J., Kasprzyk-Obara J., Short M.P., Kwiatkowski D.J.
Ann. Hum. Genet. 62:277-285(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS THR-322; ARG-587; TYR-732; SER-1035 AND SER-1108.
Tissue: Blood.
[24]"Protein truncation test for screening hamartin gene mutations and report of new disease-causing mutations."
Benit P., Kara-Mostefa A., Hadj-Rabia S., Munnich A., Bonnefont J.-P.
Hum. Mutat. 14:428-432(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TSC1 PRO-72.
[25]"Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis."
Niida Y., Lawrence-Smith N., Banwell A., Hammer E., Lewis J., Beauchamp R.L., Sims K., Ramesh V., Ozelius L.
Hum. Mutat. 14:412-422(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS THR-322; TYR-732 AND GLN-809.
Tissue: Blood and Lymphoblast.
[26]"Mutational analysis of TSC1 and TSC2 genes in Japanese patients with tuberous sclerosis complex."
Zhang H., Nanba E., Yamamoto T., Ninomiya H., Ohno K., Mizuguchi M., Takeshita K.
J. Hum. Genet. 44:391-396(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TSC1 ILE-417; GLU-654 AND SER-899, VARIANT THR-322.
Tissue: Blood.
[27]"Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation."
Van Slegtenhorst M.A., Verhoef S., Tempelaars A., Bakker L., Wang Q., Wessels M., Bakker R., Nellist M., Lindhout D., Halley D.J.J., van den Ouweland A.M.W.
J. Med. Genet. 36:285-289(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TSC1, VARIANTS.
Tissue: Peripheral blood.
[28]"Analysis of all exons of TSC1 and TSC2 genes for germline mutations in Japanese patients with tuberous sclerosis: report of 10 mutations."
Yamashita Y., Ono J., Okada S., Wataya-Kaneda M., Yoshikawa K., Nishizawa M., Hirayama Y., Kobayashi E., Seyama K., Hino O.
Am. J. Med. Genet. 90:123-126(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS THR-322; ILE-417; ASP-577 AND ARG-829.
Tissue: Peripheral blood leukocyte.
[29]"Tuberous sclerosis type 1: three novel mutations detected in exon 15 by a combination of HDA and TGGE."
Hass J., Mayer K., Rott H.-D.
Hum. Mutat. 16:88-88(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TSC1 GLN-500.
[30]"Focal cortical dysplasia of Taylor's balloon cell type: mutational analysis of the TSC1 gene indicates a pathogenic relationship to tuberous sclerosis."
Becker A.J., Urbach H., Scheffler B., Baden T., Normann S., Lahl R., Pannek H.W., Tuxhorn I., Elger C.E., Schramm J., Wiestler O.D., Bluemcke I.
Ann. Neurol. 52:29-37(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FCDBC TYR-732.
[31]"Bladder tumour-derived somatic TSC1 missense mutations cause loss of function via distinct mechanisms."
Pymar L.S., Platt F.M., Askham J.M., Morrison E.E., Knowles M.A.
Hum. Mol. Genet. 17:2006-2017(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARG-68; CYS-158; ASP-206; LEU-216 AND ILE-417, CHARACTERIZATION OF VARIANTS ARG-68; CYS-158; ASP-206; LEU-216 AND ILE-417.
[32]"Missense mutations to the TSC1 gene cause tuberous sclerosis complex."
Nellist M., van den Heuvel D., Schluep D., Exalto C., Goedbloed M., Maat-Kievit A., van Essen T., van Spaendonck-Zwarts K., Jansen F., Helderman P., Bartalini G., Vierimaa O., Penttinen M., van den Ende J., van den Ouweland A., Halley D.
Eur. J. Hum. Genet. 17:319-328(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TSC1 PRO-117; VAL-128 DEL; PRO-180; HIS-191; 198-ASN-PHE-199 DELINS ILE; ARG-224; LYS-246; ARG-305 AND TRP-305, VARIANTS GLN-509; SER-1035 AND HIS-1097, CHARACTERIZATION OF VARIANTS TSC1 PRO-117; VAL-128 DEL; PRO-180; HIS-191; 198-ASN-PHE-199 DELINS ILE; ARG-224; LYS-246; ARG-305 AND TRP-305, CHARACTERIZATION OF VARIANTS GLN-509; SER-1035 AND HIS-1097.
[33]"Functional assessment of TSC1 missense variants identified in individuals with tuberous sclerosis complex."
Hoogeveen-Westerveld M., Ekong R., Povey S., Karbassi I., Batish S.D., den Dunnen J.T., van Eeghen A., Thiele E., Mayer K., Dies K., Wen L., Thompson C., Sparagana S.P., Davies P., Aalfs C., van den Ouweland A., Halley D., Nellist M.
Hum. Mutat. 33:476-479(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TSC1 ARG-61; ILE-126; ASP-132; ILE-133; GLN-336; SER-362; ILE-411; SER-448; PRO-523; VAL-567; HIS-693; ARG-698; HIS-701; SER-762; GLY-811; THR-883; VAL-978; SER-1043 DEL AND TYR-1146, VARIANTS SER-158 AND PRO-204, CHARACTERIZATION OF VARIANTS TSC1 ARG-61; PRO-117; ILE-126; ASP-132; ILE-133; GLN-336; SER-362; ILE-411; SER-448; PRO-523; VAL-567; HIS-693; ARG-698; HIS-701; SER-762; GLY-811; THR-883; VAL-978; SER-1043 DEL AND TYR-1146, CHARACTERIZATION OF VARIANTS SER-158 AND PRO-204.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF013168 mRNA. Translation: AAC51674.1.
AK303030 mRNA. Translation: BAH13883.1.
AL445645 Genomic DNA. Translation: CAH72112.1.
CH471090 Genomic DNA. Translation: EAW88021.1.
AC002096 Genomic DNA. No translation available.
D87683 mRNA. Translation: BAA13436.1.
AF234185 Genomic DNA. Translation: AAF61948.1.
CCDSCCDS55350.1. [Q92574-2]
CCDS6956.1. [Q92574-1]
PIRT03814.
RefSeqNP_000359.1. NM_000368.4. [Q92574-1]
NP_001155898.1. NM_001162426.1.
NP_001155899.1. NM_001162427.1. [Q92574-2]
XP_005272268.1. XM_005272211.1. [Q92574-1]
XP_006717334.1. XM_006717271.1. [Q92574-1]
UniGeneHs.370854.

3D structure databases

ProteinModelPortalQ92574.
SMRQ92574. Positions 85-263.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113099. 34 interactions.
IntActQ92574. 34 interactions.
MINTMINT-1534928.
STRING9606.ENSP00000298552.

PTM databases

PhosphoSiteQ92574.

Polymorphism databases

DMDM9297077.

Proteomic databases

MaxQBQ92574.
PaxDbQ92574.
PRIDEQ92574.

Protocols and materials databases

DNASU7248.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000298552; ENSP00000298552; ENSG00000165699. [Q92574-1]
ENST00000440111; ENSP00000394524; ENSG00000165699. [Q92574-1]
ENST00000545250; ENSP00000444017; ENSG00000165699. [Q92574-2]
GeneID7248.
KEGGhsa:7248.
UCSCuc004cca.2. human. [Q92574-1]
uc011mcq.1. human. [Q92574-2]

Organism-specific databases

CTD7248.
GeneCardsGC09M135766.
GeneReviewsTSC1.
HGNCHGNC:12362. TSC1.
HPACAB011568.
CAB012481.
MIM191100. phenotype.
605284. gene.
607341. phenotype.
neXtProtNX_Q92574.
Orphanet269008. Isolated focal cortical dysplasia type IIb.
538. Lymphangioleiomyomatosis.
805. Tuberous sclerosis.
PharmGKBPA37034.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG68098.
HOGENOMHOG000232119.
HOVERGENHBG012559.
InParanoidQ92574.
KOK07206.
OMANAAMKDQ.
OrthoDBEOG7NKKJH.
PhylomeDBQ92574.
TreeFamTF325466.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkQ92574.

Gene expression databases

ArrayExpressQ92574.
BgeeQ92574.
CleanExHS_TSC1.
GenevestigatorQ92574.

Family and domain databases

InterProIPR007483. Hamartin.
[Graphical view]
PANTHERPTHR15154. PTHR15154. 1 hit.
PfamPF04388. Hamartin. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTSC1. human.
GeneWikiTSC1.
GenomeRNAi7248.
NextBio28341.
PROQ92574.
SOURCESearch...

Entry information

Entry nameTSC1_HUMAN
AccessionPrimary (citable) accession number: Q92574
Secondary accession number(s): B7Z897, Q5VVN5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1998
Last modified: July 9, 2014
This is version 141 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM